tbuckley/cabot-search huggingface dataset:
Phase 1b trial of cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic urothelial carcinoma (UC) or renal cell carcinoma (RCC).
Authors: Neeraj Agarwal, Ulka N. Vaishampayan, Bradley Alexander McGregor, Marjorie C. Green, Nehal Mohamed, Pei-Yun Chang, Thomas Powles, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

TPS541 Background: Cabozantinib (CABO) is an oral receptor tyrosine kinase inhibitor of MET, VEGFR, and TAM family receptors (TYRO3, AXL, and MER). It is approved for patients (pts) with RCC after prior therapy with antiangiogenic therapy, and has demonstrated clinical activity in UC. In clinical studies, CABO exposure increased circulating CD8+ T cells and reduced immune-suppressive monocytes and Tregs. In preclinical tumor models, CABO increased MHC class 1 expression on tumor cells and reduced myeloid-derived suppressor cells. CABO may facilitate an immune-permissive tumor environment and may enhance response to immune checkpoint inhibitors. Atezolizumab (ATEZO), an anti-PD-L1 mAb, is approved for: locally advanced/metastatic UC in pts who are cisplatin-ineligible or have disease progression during/following platinum-containing chemo; pts with metastatic NSCLC and disease progression during/following platinum-containing chemo. We present the study design of an ongoing phase 1b study combining CABO with ATEZO in pts with locally advanced/metastatic UC or RCC. Methods: This multicenter, phase 1b, open-label study aims to assess safety, tolerability, preliminary efficacy, and pharmacokinetics of CABO in combination with ATEZO (NCT03170960). The study will enroll pts with advanced UC (bladder, renal pelvis, ureter, urethra) or RCC. It consists of two stages: dose escalation and expansion. In the dose-escalation stage (3+3 design), a recommended CABO dose for the combination will be established. In the expansion stage, four tumor-specific cohorts will be enrolled: 1) pts with UC who have progressed on/after platinum-containing chemo; 2) chemo-naïve pts with UC who are cisplatin ineligible; 3) chemo-naïve pts with UC who are cisplatin eligible; and 4) untreated pts with RCC with clear cell histology; the primary objective is to determine the objective response rate in each cohort. Exploratory objectives include correlation of tumor and plasma biomarkers, and changes in immune cell profiles with clinical outcome. The study has been initiated and enrollment target is 120 pts across the 4 expansion cohorts. Clinical trial information: NCT03170960.
Tuberculin Negative?
Authors: Phyllis Q. Edwards
Journal: New England Journal of Medicine (1972)

Unexpected numbers of tuberculous patients with negative tuberculin reactions were described by Holden et al.1 in a recent issue of the Journal. Tested with several different PPD products, each used at the 5-TU (intermediate) dosage level, 17 per cent of some 115 patients with bacteriologically confirmed diagnoses of pulmonary tuberculosis failed to respond with a positive reaction to a product containing the anti-adsorbent material Tween-80, and an alarming 49 per cent to a reconstituted tableted product. Some, but by no means all, of these negative reactions could be accounted for by "extenuating clinical circumstances, such as old age, debility . . .
AB0066 MRI-Detected Osteitis Is Not Associated with The Presence or Level of ACPA Alone, but with The Combined Presence of ACPA and RF
Authors: D.M. Boeters, W.P. Nieuwenhuis, M.K. Verheul, E.C. Newsum, R.E.M. Toes, L.A. Trouw, A.H.M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> In patients with rheumatoid arthritis (RA) bone marrow edema (BME) as observed by magnetic resonance imaging (MRI) represents osteitis with infiltration of leucocytes and an increased number of osteoclasts. Both BME and anti-citrullinated protein antibodies (ACPAs) are predictors of radiographic progression in RA and recent data indicate that ACPA can directly activate osteoclasts. These findings together lead to the hypothesis that ACPA is associated with BME; indeed, two small studies observed an association between BME and ACPA. Thus far the association of ACPA with other forms of MRI-detected inflammation (synovitis and tenosynovitis) has not been thoroughly explored. Furthermore, it is unknown if the association with MRI-detected inflammation is only present for ACPA or also for other RA-related auto-antibodies. <h3>Objectives</h3> This study aimed to investigate the associations of ACPA, RF and antiCarP with BME, synovitis and tenosynovitis. <h3>Methods</h3> A total of 589 early arthritis patients, included in the Leiden Early Arthritis Clinic cohort, underwent contrast-enhanced 1.5T MRI of the unilateral wrist, metacarpophalangeal and metatarsophalangeal joints at baseline. BME, synovitis and tenosynovitis were scored according to the RAMRIS-method. ACPA, rheumatoid factor (RF) and anti-carbamylated protein (antiCarP) antibodies were determined at baseline. <h3>Results</h3> BME, synovitis and tenosynovitis were concomitantly present on MRI. In univariable analyses, ACPA-positive patients had higher BME-scores than ACPA-negative patients (median scores 4.5 vs. 2.0, p&lt;0.001), but not more synovitis and tenosynovitis. Besides ACPA, also RF (median scores 3.75 vs 2.0, p&lt;0.001) and antiCarP antibodies (median scores 3.5 vs 2.5, p=0.012) were associated with higher BME-scores in univariable analyses. To explore the association of the different antibodies with BME the BME-scores of patients with different auto-antibody combinations were compared. ACPA+RF-antiCarP- patients did not have higher BME-scores than ACPA-RF-antiCarP- patients, however ACPA+RF+antiCarP- and ACPA+RF+antiCarP+ patients had higher BME-scores (median 5.0 and 4.5 versus 2.0 respectively, p&lt;0.001 and p&lt;0.001). ACPA and RF levels were not associated with BME-scores. <h3>Conclusions</h3> The presence and the level of ACPA alone were not associated with BME-scores. However, the combined presence of ACPA and RF did associate with more BME. This suggests an additive role of RF to ACPA in mediating osteitis. <h3>Disclosure of Interest</h3> None declared
Abstract 2898: Stochastic variation in gene expression is selected during clonal evolution of spontaneous mouse mammary tumors
Authors: Sara J. Felts, Xiaojia Tang, Virginia P. Van Keulen, Krishna R. Kalari, Larry R. Pease
Journal: Cancer Research (2019)

Abstract Molecular and cellular diversity in cancer cells enables evolutionary processes that govern tumor progression and contributes to treatment failures, but the mechanisms governing this variability remain incompletely understood. We previously described tumor-specific epigenetic alterations in DNA devoid of canonical CpG methylation sites throughout the genomes of spontaneous breast tumors which arise in genetically uniform, yet heterozygous, [FVB X BALB/c MMTV-NeuT+] F1 mice. Those changes were detected in purified tumor DNA using a template-assisted quantitative ligation assay employing locus-specific and SNP-specific oligonucleotide genotyping probes, and the assay was subsequently shown to be sensitive to epigenetic modifications of the templates. We now describe losses of heterozygosity similarly distributed throughout the transcriptomes of tumors in this same model. We quantified expressed alleles across a population of clonal tumors and tested each expressed variant for the occurrence of allelic ratio outliers. The results revealed variegated patterns of expression in hundreds of genes, highly significantly enriched in pathways typically co-opted by tumors (Molecular Mechanisms of Cancer, P &amp;lt; 10-10, IPA analysis). An astounding 87% (2634 of 3044) of expressed genes that could be measured using this approach were represented in at least one tumor. Furthermore, the frequency of these outliers in any one individual tumor was found to correlate strongly with the transcriptional repression of an additional large set of non-polymorphic genes. These findings reveal underappreciated, latent mechanisms driving sporadic errors in epigenetic programming that promote repression of a multiple cis-linked transcripts. This genome-wide molecular chaos presents as dysregulated cellular homeostasis and is the foundation for heritable diversity as tumors evolve. Citation Format: Sara J. Felts, Xiaojia Tang, Virginia P. Van Keulen, Krishna R. Kalari, Larry R. Pease. Stochastic variation in gene expression is selected during clonal evolution of spontaneous mouse mammary tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2898.
Use of the Caco-2 Cell Model to Assess the Relative Lead-Chelating Ability of Diasterioisomers of 2,3-Dimercaptosuccinic Acid
Authors: Elizabeth A. Pigman, Jeri R. Lott, Quintus Fernando, James Blanchard
Journal: Environmental Health Perspectives (1999)

The purpose of this study was to examine the mechanisms of lead (Pb) uptake by human intestinal cells and to compare the intestinal transport and relative lead-chelating ability of two diastereoisomeric forms (i.e., meso and racemic) of 2, 3-dimercaptosuccinic acid (DMSA). The model used was the human adenocarcinoma (Caco-2) cell monolayer. The Caco-2 cells were cultured in flasks for examination of cellular uptake of lead and subsequent chelation of the lead by the DMSA isomers. For assessment of the comparative intestinal transport of the diastereoisomers, the Caco-2 cells were cultured on semipermeable supports. The effects of N-ethylmaleimide and 1,25-dihydroxyvitamin D3 (vitamin D3) on the uptake of lead by the Caco-2 monolayer were examined to determine the contributions of sulfhydryl-binding and calcium-binding protein, respectively, to the lead uptake process. Analysis of lead was performed using both macro- and micro-proton-induced X-ray emission (PIXE), and DMSA was measured spectrophotometrically following derivatization with 5,5'-dithiobis-2-nitrobenzoic acid. Results from micro-PIXE imaging suggest that lead is bound on the surface of the cell, and that sulfhydryl binding may be an important step in the uptake of lead by the Caco-2 cells. Macro-PIXE results indicate that the racemic form of DMSA may be more effective in chelating lead from within the cell. Comparison of the transport of the two DMSA diastereoisomers indicates that the racemic form is transported across the Caco-2 monolayer more readily than the meso form.
Carcinoma of the Pyriform Sinus
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Vaccine Preventable Deaths and the Global Immunization Vision and Strategy, 2006-2015
Journal: JAMA (2006)

Immunization is among the most successful and cost-effective public health interventions. Immunization programs have led to eradication of smallpox, elimination of measles and poliomyelitis in regions of the world, and substantial reductions in the morbidity and mortality attributed to diphtheria, tetanus, and pertussis. The World Health Organization (WHO) estimates that 2 million child deaths were prevented by vaccinations in 2003. Nonetheless, more deaths can be prevented through optimal use of currently existing vaccines. This report summarizes estimates of deaths attributed to vaccine-preventable diseases (VPDs) and vaccination coverage by WHO region and outlines the Global Immunization Vision and Strategy developed by WHO and the United Nations Children's Fund (UNICEF) and partners for implementation during 2006-2015.
Blood and plasma donations among a cohort of intravenous drug users
Authors: K. E. Nelson
Journal: JAMA (1990)

We evaluated the blood and plasma donation histories of a cohort of 2921 intravenous drug users in Baltimore, Md, and correlated these histories with their human immunodeficiency virus (HIV) serologic status, numbers of CD4 lymphocytes in the peripheral blood, and stigmata of intravenous drug use (scarred veins). Of the 793 intravenous drug users (27.1%) who had donated blood or plasma, 652 (82.2%) donated after they had started using intravenous drugs. Most subjects donated at commercial plasma centers, where they were paid $10 to $15 per donation. Although the HIV-1 seroprevalence of the entire cohort was 24.1%, the HIV-1 seroprevalence among those reporting plasma or blood donations declined progressively with time, from 17.1% in those who last donated in 1985 to 3.6% in those who last donated in 1988-1989. Many of the 437 intravenous drug users who had donated plasma or blood since 1985, when screening for HIV-1 was initiated, had not been notified and counseled about their HIV test results. Current programs to exclude individuals with a history of intravenous drug use from the plasma donor pool should be reevaluated and improved. (<i>JAMA</i>. 1990;263:2194-2197)
Comparison of alprazolam, imipramine, and placebo in the treatment of depression
Authors: J. P. Feighner
Journal: JAMA (1983)

Alprazolam is the first of the triazolobenzodiazepines to be studied in a large population of depressed patients. In a six-week, double-blind multicenter comparison of alprazolam, imipramine hydrochloride, and placebo in the treatment of 723 patients with depression, the two active drugs were statistically more effective than placebo. Alprazolam was at least as effective as imipramine in relieving depressive symptoms, significantly more effective in relieving somatic symptoms, and showed an earlier onset of activity in some measurements. Anticholinergic side effects were reported most often by patients receiving imipramine, while drowsiness was the only side effect reported most often in the alprazolam group. The Feighner Diagnostic Criteria and prestudy and poststudy intercenter conferences with videotaped patient interviews ensured interrater reliability. (<i>JAMA</i>1983;249:3057-3064)
Update: CD4+ T-Lymphocytopenia in Persons Without Evident HIV Infection—United States
Journal: JAMA (1992)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Morphological Effects of Nitrogen Dioxide on the Rat Lung
Authors: Yutaka Hayashi, Toshihiko Kohno, Hidemi Ohwada
Journal: Environmental Health Perspectives (1987)

Morphological studies of the rat lung exposed to 20 ppm NO2 for 20 hr (experiment 1), to 0.5 ppm for 19 months (experiment 2), and to 10 ppm for 14 days (experiment 3) were conducted. Changes in the mast cells of the tracheas and main bronchi of rats exposed to 0.5 ppm (experiment 4) were also observed. In the alveolus, cytoplasmic blebbing occurred in a small number of type I cells immediately after exposure to 20 ppm NO2 for 20 hr, and remarkable vacuolar change was observed 3 days after 10 ppm exposure. Exposure to 0.5 ppm did not cause degeneration. Swelling and hyperplasia of type II cells were observed. The cells gradually became flat and began a transition from type II to type I cells. These intermediate-type cells were noticed in experiments 1 and 2, but no intermediate-type cells were found in experiment 3. In each experiment, pinocytotic vesicles of endothelial cells in capillaries, followed by interstitial edema in the alveolar walls, were observed. In addition to these changes, desquamation of endothelium and widening of the endothelial junction of endothelial cells occurred in experiment 3. The early changes observed in the animals exposed to 0.5 ppm NO2 were the numerical and histochemical changes of mast cells in the trachea and main bronchus.
Hepatocyte proliferative activity in chronic liver damage as assessed by the monoclonal antibody MIB1 Ki67 in archival material: The role of etiology, disease activity, iron, and lipid peroxidation
Authors: F Farinati
Journal: Hepatology (1996)

Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related liver damage is linked to an increased risk of hepatocellular carcinoma, but the mechanisms underlying hepatitis C viral activity are not known. We therefore compared hepatocellular proliferative activity in chronic C virus-related hepatitis and in liver damage of other etiology. Hepatocyte proliferation rate was investigated in 56 patients with chronic hepatitis using the Ki67 MIB1 monoclonal antibody in archival material. According to etiology, the patients were subgrouped as follows: HCV (34), HBV (11), Alcohol (4), HCV + Alcohol (4), and Hemochromatosis (3). Proliferation rate was correlated with age, sex, etiology, disease activity, liver iron storage, free-radical production, and glutathione levels by regression and discriminant analysis. HCV-positive patients had significantly more MIB1-positive hepatocytes in the periportal area (P < .011) and in the low-proliferating perivenular area (zones 2 and 3) (P < .05). The number of MIB1-positive cells correlated directly with alanine transaminase (ALT) levels, Knodell index (KI), and, inversely, with iron saturation. By stepwise discriminant analysis, ALT levels and etiology were identified as single independent variables. These data suggest that HCV infection induces increased and abnormal hepatocyte proliferation, which might be related to the increased risk of hepatocellular carcinoma in patients with HCV-related liver damage.
Gibbon's Surgery of the Chest
Authors: William A. Gay
Journal: JAMA (1976)

Since the first edition of this text, published in 1962, it has been the standard against which all other texts dealing with similar subject matter have been compared. The style with which each contribution is written (that is, a brief historical sketch followed by a descriptive text and a complete and current reference list) makes this volume equally suitable for medical students, house officers, and fully trained thoracic surgeons. The third edition has greatly expanded the section on coronary disease, including separate authoritative chapters dealing with arteriography, circulatory assistance, cardiac arrest and resuscitation, dietary and pharmacologic therapy of atherosclerosis, and the therapeutic effectiveness of ileal bypass in the prevention of atherosclerosis. Those chapters dealing with the surgical treatment of coronary disease and its complications are exceptionally well written and illustrated. The section devoted to cardiothoracic surgery in the pediatric age group has also been expanded. I do not believe there
Informed consent waiver for emergency research
Authors: C. Marwick
Journal: JAMA (1995)

THE REQUIREMENT for informed consent from subjects participating in some types of clinical experimental studies is in the process of being waived. The Food and Drug Administration (FDA) is proposing ways to make it easier for drugs and devices to be tested under life-threatening situations where the patient is unable to give consent to participate in research. The action is prompted by growing concern that the current rules, as they are interpreted, are "making high quality acute care research difficult or impossible to carry out at a time when the need for such research is increasingly recognized," said the FDA in announcing the proposed rule. The proposal is designed to amend the rule for drug and device testing in circumstances where the patient is unable to give informed consent. It provides that an independent physician and the institutional review board (IRB) granting approval of such research agree that the study
Incorrect Value
Journal: JAMA (1985)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cover Page
Journal: Cardiovascular Research (2013)

The myofibril structure of the cardiomyocytes isolated from 3-day-old Sprague-Dawley neonatal rats.(H ) A cell in which the striated alpha-actinin pattern (red) is co-localized with the SHG signal pattern both in the cell centre and at the cell edge in the middle of the myofibrils.(I ) Magnification of the area surrounded by the white bracket in H.The yellow arrowheads in G-I point to the short-term Z-bodies of premyofibrils.See figure legend on page 267.Regulation of PKG-I Neutrophil TRPM2 channels in I/R injury Parthenogenetic ES cells ameliorate post-MI remodeling C5a-mediated mast cell activation in vein graft disease O-GlcNAc and cardioprotection in diabetic patients